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基于生信分析预测人参-茯苓药对治疗结直肠癌的分子机制*(PDF)

《云南中医学院学报》[ISSN:1000-2723/CN:53-1048/R]

期数:
2019年03期
页码:
83-92
栏目:
方药研究
出版日期:
2020-04-20

文章信息/Info

Title:
Prediction of Molecular Mechanism of Ginseng-Indian Bread in the Treatment of Colorectal Cancer Based on Biosignal Analysis
文章编号:
1000-2723（2019）03-0083-10
作者:
周小英1; 苗大兴2△; 符中柱2; 龚超超1; 袁盛兰1; 熊 浩1
（1. 贵州中医药大学，贵州 贵阳 550002；2. 贵州中医药大学第一附属医院，贵州 贵阳 550001）
Author(s):
ZHOU Xiaoying1;  MIAO Daxing2;  FU Zhongzhu2;  GONG Chaochao1;  YUAN Shenglan1;  XIONG Hao1
(1. Guizhou University of Traditional Chinese Medicine, Guiyang 550002,China; 2. The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001,China)
关键词:
人参-茯苓; 结直肠癌; 生物信息分析; 靶点; 信号通路
Keywords:
Ginseng-Indian Bread;  colorectal cancer;  bioinformatics analysis;  target;  signaling pathway
分类号:
R285.5
DOI:
10.19288/j.cnki.issn.1000-2723.2019.03.0014
文献标识码:
A
摘要:
目的通过生物信息分析获取人参-茯苓药对治疗疾病的潜在靶点基因，挖掘结直肠癌患者和健康人的基因数据芯片，预测人参、茯苓药对治疗结直肠癌的潜在机制。方法 从GEO数据库中获取GSE128449基因芯片，使用GEO2R在线分析软件设置P＜0.01，log2FC＞1.5，得出差异基因。从中药分子机制的生物信息学分析工具BATMAN-TCM(A Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine)设置预测候选目标积分＞20，P＜0.05，获得人参-茯苓药对的化合物和可能干预的靶基因数，两者取交集获得药对治疗结直肠癌的靶点基因。使用PPI分析数据库STRING构建靶点互作（PPI）网络模型，采用Cyotoscape作图软件构建网络，利用CytoHubba插件进行Hub（核心）基因网络分析，采用R语言的Bioconductor包进行通路富集（KEGG）分析和生物过程（GO）分析。结果 本实验从GEO2R中共获得CRC显著性高的基因890个（P<0.05），从BATMAN-TCM数据库中获得人参（Ginseng）293个化合物（其中138个化合物无结构信息），可能干预的靶基因1338个。茯苓（Indian Bread）共54个化合物（其中33个化合物无结构信息），可能干预的靶基因503个。两者交集共获得23个基因，分别为LEP、APOE、HTR3A、NPPA、TNF、PTGS2、 HMBS、CREB1、AKR1C1、NFKB1、COX5A、RXRA、CAMK2D、PPARG、 HDAC9、GABRA2、IL6、MAOB、NFIB、RAB3B、GRIN1、ADK、RRM2B。这些基因主要参与了代谢过程的积极调节，炎症反应、细胞凋亡、细胞死亡、细胞增殖的负调节等GO生物过程。主要调控TNF信号通路、PI3K/Akt信号通路、NF-κB信号通路及癌症中的转录失调途径等。结论 人参-茯苓可能通过干预TNF、NFKB1、IL6、PTSG2等调控癌症相关和炎症相关途径来防治结直肠癌。
Abstract:
Objective To obtain the potential target genes of ginseng-Indian Bread drugs for treating diseases through bioinformatics analysis, and to mine the genetic data chips of colorectal cancer patients and healthy people, and to predict the potential mechanism of ginseng-Indian Bread drugs for the treatment of colorectal cancer. Methods The GSE128449 gene chip was obtained from GEO database. The GEO2R online analysis software was used to set P<0.01, log2FC>1.5, and the differential genes were obtained. The bioinformatics analysis tool BATMAN-TCM (A Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine) set the candidate target score >20, P<0.05, obtained the compounds and target genes of ginseng-Indian Bread pair that may be interfered, and the two take the intersection to obtain the target genes for colorectal cancer. The target interaction(PPI) network model was constructed by using the PPI analysis database STRING, the network was constructed by using Cyotoscape mapping software, the Hub (core) gene network analysis was performed by the CytoHubba plug-in, and the path enrichment (KEGG) analysis and biological process (GO) analysis were performed by the R language Bioconductor package. Results In this experiment, 890 genes with high CRC significance(P<0.05) were obtained from GEO2R, and 293 compounds of Ginseng were obtained from BATMAN-TCM database (138 compounds had no structural information), and 1338 target genes might be interfered. Indian Bread acquired 54 compounds (33 of which have no structural information) may be involved in 503 target genes. A total of 23 genes were obtained including LEP, APOE, HTR3A, NPPA, TNF, PTGS2, HMBS, CREB1, AKR1C1, NFKB1, COX5A, RXRA, CAMK2D, PPARG, HDAC9, GABRA2, IL6, MAOB, NFIB, RAB3B, GRIN1, ADK, RRM2B. These genes were involved in the GO biological process such as active regulation of metabolic processes, regulation of inflammatory response, apoptosis, cell death, and negative regulation of cell proliferation. Also they regulate TNF signaling pathway, PI3K/Akt Signal pathways, NF-κB signaling pathways and transcriptional disorders in cancer. Conclusion Ginseng-Indian Bread may prevent and treat colorectal cancer by interfering with TNF, NFKB1, IL6, PTSG2 and other cancer-related and inflammation-related pathways.

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备注/Memo

备注/Memo:
收稿日期： 2019 - 03- 08
* 基金项目： 2018年度全国中医药研究生教育研究课题（23）
第一作者简介： 周小英（1990-），女，在读硕士研究生，研究方向：中西医结合防治结直肠疾病。
△通信作者： 苗大兴，E-mail：740916216@qq.com
更新日期/Last Update: 2020-05-06